SB-271,046

SB-271,046
IUPAC ime
5-hloro-N-(4-metoksi-3-piperazin-1-ilfenil)-3-metil-1-benzotiofen-2-sulfonamid
Identifikatori
ATC kodnone
PubChemCID 5312149
IUPHAR/BPS276
ChEMBLCHEMBL431298 ДаY
Hemijski podaci
FormulaC20H22ClN3O3S2
Molarna masa451,989 g/mol
  • C4CNCCN4c3cc(ccc3OC)NS(=O)(=O)c1sc2ccc(Cl)cc2c1C

SB-271,046 je lek koji se koristi u naučnim istraživanjima. On je bio jedan od prvih selektivnih antagonista 5-HT6 receptora.[1] SB-271,046 je potentan i selektivan in vitro i dobrom oralnom biodostupnošću in vivo, ali ima slabu penetraciju kroz krvno moždanu barijeru, te su razvijeni poboljšani 5-HT6 antagonisti kao što su SB-357,134 i SB-399,885.[2]

SB-271,046 povišava nivoe ekscitatornih aminokiselinskih neurotransmitera glutamata i aspartata,[3] kao i dopamina i noradrenalina[4] u frontalnom korteksu i hipokampusu pacova.[5] Pokazano je da 5-HT6 antagonisti proizvode nootropne efekte u brojnim studijama na životinjama.[6][7][8] Smatrase da ovaj lekovi ove klase mogu da nađu primenu u tretmanu šizofrenije i drugih psihijatrijskih poremećaja.[9][10][11][12]

Reference

  1. ^ Bromidge, SM; Brown, AM; Clarke, SE; Dodgson, K; Gager, T; Grassam, HL; Jeffrey, PM; Joiner, GF; King, FD (1999). „5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046): a potent, selective, and orally bioavailable 5-HT6 receptor antagonist”. Journal of Medical Chemistry. 42 (2): 202—5. PMID 9925723. doi:10.1021/jm980532e. 
  2. ^ Ahmed, M; Briggs, MA; Bromidge, SM; Buck, T; Campbell, L; Deeks, NJ; Garner, A; Gordon, L; Hamprecht, DW (2005). „Bicyclic heteroarylpiperazines as selective brain penetrant 5-HT6 receptor antagonists”. Bioorganic & Medicinal Chemistry Letters. 15 (21): 4867—71. PMID 16143522. doi:10.1016/j.bmcl.2005.06.107. 
  3. ^ Dawson, LA; Nguyen, HQ; Li, P (2000). „In vivo effects of the 5-HT6 antagonist SB-271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5-HT, glutamate and aspartate”. British Journal of Pharmacology. 130 (1): 23—6. PMC 1572041 Слободан приступ. PMID 10780993. doi:10.1038/sj.bjp.0703288. 
  4. ^ Lacroix, LP; Dawson, LA; Hagan, JJ; Heidbreder, CA (2004). „5-HT6 receptor antagonist SB-271046 enhances extracellular levels of monoamines in the rat medial prefrontal cortex”. Synapse. 51 (2): 158—64. PMID 14618683. S2CID 6539467. doi:10.1002/syn.10288. 
  5. ^ Dawson, LA; Nguyen, HQ; Li, P (2001). „The 5-HT(6) receptor antagonist SB-271046 selectively enhances excitatory neurotransmission in the rat frontal cortex and hippocampus”. Neuropsychopharmacology. 25 (5): 662—8. PMID 11682249. S2CID 25358343. doi:10.1016/S0893-133X(01)00265-2. 
  6. ^ Rogers, DC; Hagan, JJ (2001). „5-HT6 receptor antagonists enhance retention of a water maze task in the rat”. Psychopharmacology. 158 (2): 114—9. PMID 11702084. S2CID 29472459. doi:10.1007/s002130100840. 
  7. ^ Foley, AG; Murphy, KJ; Hirst, WD; Gallagher, HC; Hagan, JJ; Upton, N; Walsh, FS; Regan, CM (2004). „The 5-HT(6) receptor antagonist SB-271046 reverses scopolamine-disrupted consolidation of a passive avoidance task and ameliorates spatial task deficits in aged rats”. Neuropsychopharmacology. 29 (1): 93—100. PMID 14571256. S2CID 21898284. doi:10.1038/sj.npp.1300332. 
  8. ^ Marcos, B; Chuang, TT; Gil-Bea, FJ; Ramirez, MJ (2008). „Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat”. British Journal of Pharmacology. 155 (3): 434—40. PMC 2567877 Слободан приступ. PMID 18622410. doi:10.1038/bjp.2008.281. 
  9. ^ Minabe, Y; Shirayama, Y; Hashimoto, K; Routledge, C; Hagan, JJ; Ashby Jr, CR (2004). „Effect of the acute and chronic administration of the selective 5-HT6 receptor antagonist SB-271046 on the activity of midbrain dopamine neurons in rats: an in vivo electrophysiological study”. Synapse. 52 (1): 20—8. PMID 14755629. S2CID 25687099. doi:10.1002/syn.20002. 
  10. ^ De Foubert, G; O'Neill, MJ; Zetterström, TS (2007). „Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression”. Neuroscience. 147 (3): 778—85. PMID 17560041. S2CID 37184427. doi:10.1016/j.neuroscience.2007.04.045. 
  11. ^ Marcos, B; Aisa, B; Ramírez, MJ (2008). „Functional interaction between 5-HT(6) receptors and hypothalamic-pituitary-adrenal axis: cognitive implications”. Neuropharmacology. 54 (4): 708—14. PMID 18206183. S2CID 21417069. doi:10.1016/j.neuropharm.2007.11.019. 
  12. ^ Loiseau, F; Dekeyne, A; Millan, MJ (2008). „Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex”. Psychopharmacology. 196 (1): 93—104. PMID 17922111. S2CID 35795618. doi:10.1007/s00213-007-0934-5. 

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